Telomerase (hTERT) reactivation and sustained expression is a key event in the process of cellular transformation. Therefore, the identification of the mechanisms regulating hTERT expression is of great interest for the development of new anticancer therapies. Although the epigenetic state of hTERT gene promoter is important, we still lack a clear understanding of the mechanisms by which epigenetic changes affect hTERT expression. Retinoids are well-known inducers of granulocytic maturation in acute promyelocytic leukemia (APL). We have previously shown that retinoids repressed hTERT expression in the absence of maturation leading to growth arrest and cell death. Exploring the mechanisms of this repression, we showed that transcription factor binding was dependent on the epigenetic status of hTERT promoter. In the present study, we used APL cells lines and publicly available datasets from APL patients to further investigate the integrated epigenetic events that promote hTERT promoter transition from its silent to its active state, and inversely. We showed, in APL patients, that the methylation of the distal domain of hTERT core promoter was altered and correlated with the outcome of the disease. Further studies combining complementary approaches carried out on APL cell lines highlighted the significance of a domain outside the minimal promoter, localized around 5 kb upstream from the transcription start site, in activating hTERT. This domain is characterized by DNA hypomethylation and H3K4Me3 deposition. https://www.selleckchem.com/products/stat-in-1.html Our findings suggest a cooperative interplay between hTERT promoter methylation, chromatin accessibility, histone modifications that force the revisiting of previously proposed concepts regarding hTERT epigenetic regulation. They represent, therefore, a major advance in predicting sensitivity to retinoid-induced hTERT repression and, more generally, in the potential development of therapies targeting hTERT expression in cancers. This article is protected by copyright. All rights reserved.Nivolumab, a fully human IgG4 immune checkpoint modulator, binds to the programmed cell death 1 (PD-1) receptor on T cells and blocks their inhibition. Thus, it increases the anticancer host immune response by allowing T cells to attack tumor cells. Although anti-PD-1 immunotherapy is typically well accepted, deregulation of immune tolerance caused by nivolumab may determine immune-related adverse events, among which skin toxicities represent the most common. We report a case of severe new-onset palmoplantar and nail psoriasis after receiving nivolumab treatment for metastatic melanoma. © 2020 Wiley Periodicals LLC.As a potential antitumor herbal medicine, plantamajoside (PMS) benefits the treatment of many human malignances. However, the role of PMS in the progression of hepatocellular carcinoma (HCC) and the related molecular mechanisms is still unknown. Here, we proved that the cell viabilities of&nbsp;HepG2 cells were gradually decreased with the increasing concentrations of CoCl2 and/or PMS via cell counting kit-8 assay. Meanwhile, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and western blot assays were used to further confirm that PMS inhibited the CoCl2 -induced cell proliferation in HepG2 cells via suppressing the Ki67 and proliferating cell nuclear antigen expressions. We also performed wound-healing and transwell assays and demonstrated that PMS inhibited CoCl2 -induced migration and invasion in HepG2 cells via suppressing the epithelial-mesenchymal transition (EMT) process. In addition, the use of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole further proved that PMS inhibited the malignant biological behaviors of HepG2 cells under hypoxic condition by suppressing the hypoxia-inducible factor-1α (HIF-1α) expression. Besides, we further confirmed that PMS suppressed the growth and metastasis of implanted tumors in vivo. Given that PMS suppressed the proliferation and EMT induced by CoCl2 in HCC cells via downregulating HIF-1α signaling pathway, we provided evidence that PMS might be a novel anti-cancer drug for HCC treatment. © 2020 International Federation for Cell Biology.In late life, traumas may act cumulatively to exacerbate vulnerability to post-traumatic stress disorder (PTSD). PTSD is also a risk factor for cognitive decline. Major neurocognitive disorder (MND) can be associated with worsening of already controlled PTSD symptoms, late-life resurgence or de novo emergence. Misidentifying PTSD symptoms in MND can have negative consequences for the patient and families. We review the literature pertaining to PTSD and dementia and describe five cases referred for consultation in geriatric psychiatry initially for behavioural and psychological symptoms of dementia (BPSD), which were eventually diagnosed and treated as PTSD in MND subjects. We propose that certain PTSD symptoms in patients with MND are misinterpreted as BPSD and therefore, not properly addressed. For example, flashbacks could be interpreted as hallucinations, hypervigilance as paranoia, nightmares as sleep disturbances, and hyperreactivity as agitation/aggression. We suggest that better identification of PTSD symptoms in MND is needed. We propose specific recommendations for care, namely clarifying diagnosis by distinguishing PTSD symptoms coexisting with different types of dementia from a specific dementia symptom (BPSD), gathering a detailed history of the trauma in order to personalise non-pharmacological interventions, adapting psychotherapeutic strategies to patients with dementia, using selective serotonin reuptake inhibitors as first-line treatment and avoiding antipsychotics and benzodiazepines. Proper identification of PTSD symptoms in patients with MND is essential and allows a more tailored and efficient treatment, with decrease in inappropriate use of physical and chemical restraints. © 2020 Japanese Psychogeriatric Society.Intensive crop production systems worldwide, particularly in China, rely heavily on nitrogen (N) fertilization, but left more than 50% of it in the environment. Nitrogen (over)fertilization and atmospheric N deposition induce soil acidification, which is neutralized by soil inorganic carbon (SIC; carbonates) and carbon dioxide (CO2 ) is released to the atmosphere. For the first time, the loss of SIC stocks in response to N-induced soil acidification was estimated from Chinese croplands from 1980 to 2020 and forecasts were made up to 2100. The SIC stocks in croplands in 1980 were 2.16 Pg C (16.3 Mg C ha-1 ) in the upper 40 cm, 7% (0.15 Pg C; 1.1 Mg C ha-1 ) of which were lost from 1980 to 2020. During these 40 years, 7 million ha of cropland has become carbonate free. Another 37% of the SIC stocks may be lost up to 2100 in China, leaving 30 million ha of cropland (37.8%) without carbonates if N fertilization follows the business as usual (BAU) scenario. Compared to the BAU scenario, the reduction of N input by 15%-30% after 2020 (scenarios S1 and S2) will decrease carbonates dissolution by 18%-41%.